Polygenic Architecture of Common Severe Hypertriglyceridemia

[See article vol.27: 1264-1277] Severe hypertriglyceridemia usually accompanies hyperchylomicronemia and is classified into types I and V hyperlipidemia characterized by an increase in chylomicrons alone and an increase in both chylomicrons and very-low-density lipoproteins (VLDLs), respectively. The extremely rare, monogenic form of hyperchylomicronemia is often referred as familial chylomicronemia syndrome (FCS) that usually manifests as type I hyperlipidemia during childhood or adolescence. The genetic basis of FCS has been extensively investigated, revealing that the primary underlying causes common to FCS are critical defects in the lipolytic function of lipoprotein lipase (LPL), a crucial rate-limiting enzyme for hydrolysis of triglycerides (TG) in both chylomicrons and VLDLs. Accordingly, monogenic, recessive disease-causing mutations have been found in LPL itself or other genes essential for LPL function (such as APOC2, APOA5, GPIHBP1, and LMF1) in the majority of FCS patients. Although FCS is a very rare clinical condition that is found in approximately 1～10 patients in a million people, severe hypertriglyceridemia can be more frequently experienced in general clinics or hospitals, typically in adult patients with type V hyperlipidemia.